The exact molecular mechanisms involved in the catabolism of enkephalin are still unclear, but various reports strongly suggest that Tyr-Gly-Gly may be a major metabolite produced by the action of an exopeptidase such as carboxypeptidase or dipeptidyl carboxypeptidase. In order to test which exopeptidase is involved in the catabolism of enkephalin, we have studied the effect of dipeptidyl carboxypeptidase inhibitor, captopril, on the rate of disappearance of intraventricularly injected enkephalin and on endogenous brain enkephalin content. The drug prolongs the half life of injected enkephalin and potentiates the analgesic effect of the injected enkephalin but fails to change the content of endogenous enkephalin in either control or stressed animals. These results suggest that dipeptidyl carboxypeptidase may not be involved in the catabolism of enkogenous endephalin. We are currently studying the effect of a carboxypeptidase A inhibitor on the enkephalin content of various brain parts of normal and stressed rats.